Impact of cerebral small vessel disease burden and drug level at admission on direct oral anticoagulant associated intracerebral hemorrhage.

INTRODUCTION: Direct oral anticoagulant (DOAC)-associated intracerebral hemorrhage (ICH) is a catastrophic complication. The aim of this study was to investigate the association between computed tomography (CT)-based cerebrovascular small vessel disease (SVD) burden and DOAC-ICH as well as the DOAC concentration upon hospital admission and ICH outcome. PATIENTS AND METHODS: The study included two cohorts: (1) DOAC-ICH: patients who suffered from DOAC-ICH and underwent drug level measurements upon admission; (2) DOAC-non-ICH: stable DOAC users who underwent head CT without ICH during treatment. We categorized the DOAC levels of the DOAC-ICH patients as low (<50 ng/mL), medium (50-300 ng/mL), and high (>300 ng/mL). The CT-based SVD burden (including white matter lesions [WML], lacunes, and cerebral atrophy) was evaluated, and SVD scores (range, 0-3) were used to evaluate SVD severity. RESULTS: A total of 43 DOAC-ICH patients and 177 DOAC-non-ICH patients were enrolled. DOAC-ICH patients were more likely to have WML, lacunes, or cerebral atrophy compared to DOAC-non-ICH patients. After adjustment, the SVD burden was associated with DOAC-ICH, with a higher risk of more severe SVD (SVD score of 2; odds ratio [OR], 10.3 [3.17, 33.3]; score of 3; OR, 16.8 [4.50, 62.6]). The proportions of patients with high, medium, and low drug levels in the DOAC-ICH group were 16.3%, 55.8%, and 27.9%, respectively. Additionally, the high-level group displayed a larger hematoma size and had worse functional outcomes at 3 months than the other two groups. DISCUSSION AND CONCLUSION: The severity of SVD burden was associated with DOAC-ICH. Furthermore, high DOAC levels in ICH were associated with unfavorable clinical outcomes. To address the potential selection bias from these two cohorts, a prospective study to investigate the co-contribution of drug levels and SVD to DOAC-ICH is essential.

The association between direct oral anticoagulant concentration upon acute stroke and stroke outcome.

BACKGROUND: This study aimed to investigate the association between direct oral anticoagulant (DOAC) concentration upon acute ischemic stroke (IS) or intracranial hemorrhage (ICH) and stroke outcomes. METHODS: Patients aged ≥20 years treated with DOACs, including dabigatran, rivaroxaban, apixaban, or edoxaban, and developed acute IS or ICH were enrolled to measure DOAC concentration at the time of hospital presentation by using ultrahigh-performance liquid chromatography with tandem mass spectrometry. Ischemic stroke patients was categorized into low (<50 ng/mL) and effective (≥50 ng/mL) groups. The primary outcome was poor functional outcomes at 3 months (modified Rankin Scale scores of 4-6). RESULTS: A total of 138 patients were enrolled, including 105 IS (76.1%) and 33 ICH patients. In the IS cohort, the average DOAC concentration was 85.7 ± 88.6 ng/mL (low DOAC concentration: 42.9%). Low level group had numerically higher NIHSS (14 versus 9, p = 0.37), significantly poorer functional outcomes at 3 months (odds ratio [OR], 5.08 [1.32, 19.63]), and higher chance of stroke-in-evolution (OR, 6.83 [1.64, 28.41]). In the ICH cohort, the average DOAC concentration was 128.9 ± 111.9 ng/mL. Reversal therapy was administered in 60.6% of patients. Hematoma growth occurred in 35.7% patients. The DOAC concentration was similar across patients with or without reversal therapy, and with or without hematoma growth. CONCLUSION: Among DOAC users who developed IS, low drug concentrations at hospital presentation predicted poor outcomes.

Higher infection of dengue virus serotype 2 in human monocytes of patients with G6PD deficiency.

The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency is high in Asia. An ex vivo study was conducted to elucidate the association of G6PD deficiency and dengue virus (DENV) infection when many Asian countries are hyper-endemic. Human monocytes from peripheral mononuclear cells collected from 12 G6PD-deficient patients and 24 age-matched controls were infected with one of two DENV serotype 2 (DENV-2) strains-the New Guinea C strain (from a case of dengue fever) or the 16681 strain (from a case of dengue hemorrhagic fever) with a multiplicity of infection of 0.1. The infectivity of DENV-2 in human monocytes was analyzed by flow cytometry. Experimental results indicated that the monocytes of G6PD-deficient patients exhibited a greater levels of infection with DENV-2 New Guinea C strain than did those in healthy controls [mean+/-SD:33.6%+/-3.5 (27.2% approximately 39.2%) vs 20.3%+/-6.2 (8.0% approximately 30.4%), P<0.01]. Similar observations were made of infection with the DENV-2 16681 strain [40.9%+/-3.9 (35.1% approximately 48.9%) vs 27.4%+/-7.1 (12.3% approximately 37.1%), P<0.01]. To our knowledge, this study demonstrates for the first time higher infection of human monocytes in G6PD patients with the dengue virus, which may be important in increasing epidemiological transmission and perhaps with the potential to develop more severe cases pathogenically.